Arteriosclerosis, the group of diseases characterized by plaque deposition and gradual blockage of blood flow in arterial vessels, may result in ischemia of the heart, brain or extremities, resulting in infarction and sometimes death. Over 2,000,000 vascular interventions are performed each year worldwide with over 800,000 of these being performed in the United States. Since about 1977, blocked arteries have been treated using a balloon catheter. This procedure, known as percutaneous transluminal angioplasty (PTA), involves the insertion of a catheter into the lumen of a blocked artery and the inflation of an attached balloon to open the artery (both coronary and non-coronary vessels). Another catheter procedure, commonly known as atherectomy, opens a blocked artery by grinding or cutting plaque deposits and suctioning the deposits from the artery. More recently, metal structures called stents have been placed in the affected artery to keep the previously blocked artery open after PTA or atherectomy treatment. Presently, over 70% of persons currently treated for arterial lesions have implanted stents.
It is fortunate that over 90% of coronary interventions are successful in opening the blocked artery. However, the later renarrowing of the opened artery, (i.e. restenosis) remains a significant problem. Unfortunately, within six months after a first PTA or atherectomy treatment, restenosis occurs in about 30% to 50% of patients. When restenosis occurs, either another PTA or atherectomy treatment is performed, and another stent is implanted, or bypass surgery is performed. After a second catheter procedure, restenosis occurs in about 60% of patients, who then must undergo yet another catheter procedure or submit to bypass surgery.
Though many details of restenosis remain unclear, the general consensus is that angioplasty and stenting, either individually or collectively, cause a stretch and tear injury to the arterial wall which results in an inflammation that leads to the activation of multiple cell lines. In particular, there is concern for the monocyte/macrophage line. Specifically, it is known that monocytes will migrate to the area of an arterial injury. There, they differentiate into tissue macrophages and secrete cytokines and growth factors which cause the migration and proliferation of smooth muscle cells into the area. This results in excessive tissue growth or restenosis.
Not surprisingly, efforts have been taken to prevent restenosis. For example, medications such as calcium channel blockers, corticosteroids, antiplatelet agents, fish oils, lovastatin and anticoagulants have been tried in attempts to prevent restenosis. Heretofore, however, these efforts have been generally unsuccessful. Radiation therapy has been shown to reduce restenosis, but radiation therapy is generally impractical because it is time consuming, requires specialized equipment, specialized personnel, and is often difficult to arrange. Some immunosuppressants, on the other hand, show promise.
It is known that the immunosuppressant medication 2-chloro-deoxyadenosine (2-CdA) is selectively toxic to monocytes, and is effective in lowering monocyte levels in humans. Presently, this medication (2-CdA) has been FDA approved for use in the treatment of hairy cell leukemia, and also has activity in cutaneous T-cell lymphoma, myeloid leukemias, chronic lymphocytic leukemia, Langerhans cell histiocytosis and non-Hodgkin's lymphoma. Additionally, FDA approval has been sought for treatment of multiple sclerosis. As a new and useful application, the present invention discloses a method of preventing restenosis by administering a therapeutically effective dose of 2-CdA.
In light of the above, it is an object of the present invention to provide a method for preventing a restenosis in the vasculature of a patient which promotes a systemic suppression to the inflammation response that provokes a restenosis. Another object of the present invention is to provide a method for preventing a restenosis in the vasculature of a patient which uses a medication that can be administered orally, subcutaneously, intravenously, intramuscularly, or topically. Yet another object of the present invention is to provide a method for preventing restenosis in the vasculature of a patient which minimizes adverse side effects and, thus, is minimally intrusive into a patient's life style and quality of life. It is still another object of the present invention to provide a method for preventing a restenosis in the vasculature of a patient which uses a medication that is relatively easy to administer, is effective for its intended purpose, and is comparatively cost effective.